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Biomedical subjects

G R Cooper

Publications and source records attributed to G R Cooper.

At least 19 recordsLinked to original sources
PubMed1992

Blood lipid measurements. Variations and practical utility.

OBJECTIVE: To describe the magnitude and impact of the major biological and analytical sources of variation in serum lipid and lipoprotein levels on risk of coronary heart disease; to present a way to qualitatively estimate the total intraindividual variation; and to demonstrate how to determine the number of specimens required to estimate, with 95% confidence, the "true" underlying total cholesterol value in the serum of a patient. DATA SOURCES: Representative references on each source of variation were selected from more than 300 reviewed publications, most published within the past 5 years, to document current findings and concepts. Most articles reviewed were in English. STUDY SELECTIONS: Studies on biological sources of variation were selected using the following criteria: representative of published findings, clear statement of either significant or insignificant results, and acquisition of clinical and laboratory data under standardized conditions. Representative results for special populations such as women and children are reported when results differ from those of adult men. DATA EXTRACTION: References were selected based on acceptable experimental design and use of standardized laboratory lipid measurements. DATA SYNTHESIS: The lipid levels considered representative for a selected source of variation arose from quantitative measurements by a suitably standardized laboratory. Statistical analysis of data was examined to assure reliability. The proposed method of estimating the biological coefficient of variation must be considered to give qualitative results, because only two or three serial specimens are collected in most cases for the estimation. CONCLUSIONS: Concern has arisen about the magnitude, impact, and interpretation of preanalytical as well as analytical sources of variation on reported results of lipid measurements of an individual. Preanalytical sources of variation from behavioral, clinical, and sampling sources constitute about 60% of the total variation in a reported lipid measurement of an individual. A technique is presented to allow physicians to qualitatively estimate the intraindividual biological variation of a patient from the results of two or more specimens reported from a standardized laboratory and to determine whether additional specimens are needed to meet the National Cholesterol Education Program recommendation that the intraindividual serum total cholesterol coefficient of variation not exceed 5.0. A National Reference Method Network has been established to help solve analytical problems.

Analysis of Variance↗
PubMed1992

Intracardiac detection of angiotensinogen and renin: a localized renin-angiotensin system in neonatal rat heart.

There is increasing evidence that the renin-angiotensin system (RAS) modulates cardiovascular function through both blood-borne and tissue-derived components. The existence of a local RAS has been proposed in the heart based on biochemical and molecular biological studies that identify angiotensinogen and renin. We conducted the present study to determine the chamber localization of angiotensinogen and renin mRNA in neonatal rat heart and whether these components could be identified in cultured cardiomyocytes and fibroblasts obtained from neonatal rat heart. Experiments using polymerase chain reaction (PCR) indicated that whole hearts obtained from neonatal rats contained both angiotensinogen and renin mRNA. With the use of radiolabeled cDNA probes and in situ hybridization, angiotensinogen and renin transcripts were localized both in the atria and ventricles of neonatal rat hearts. Relative signal strengths for angiotensinogen were highest in the left and right ventricles. In contrast, renin signal strength was overall much lower and preferentially localized in the left ventricle. To investigate the cellular source of angiotensinogen and renin, cultured neonatal heart cardiomyocytes and ventricular fibroblasts were screened for angiotensinogen and renin messenger RNA and protein using PCR and indirect immunofluorescent staining, respectively. These experiments demonstrated that both cell types produce transcripts and the respective translation products for angiotensinogen and renin. These data suggest that the site of angiotensin II synthesis can occur at the level of the individual cardiomyocyte and fibroblast, where it may serve to directly and/or indirectly regulate cardiac rate, force, growth, and development in the neonate.

Angiotensinogen↗
PubMed1992

Detection of angiotensin I and II in cultured rat cardiac myocytes and fibroblasts.

Angiotensin II (ANG II) is a stimulus for positive chronotropic and inotropic effects, protein synthesis, and hypertrophic growth in cardiac tissue. These short- and long-term effects of ANG II are mediated through specific plasma membrane receptors. Indirect evidence suggests that ANG II synthesized in the myocardium may be important in regulating cardiac function. The cell types in the myocardium that produce components of the renin-angiotensin system have not been determined. In this study, we evaluated whether cultured cardiomyocytes and fibroblasts obtained from ventricles of neonatal rat hearts were capable of synthesizing ANG I and II. Both cardiomyocytes and fibroblasts were found to have immunofluorescent staining for ANG I, ANG II, and angiotensin-converting enzyme (ACE). The amounts of ANG I and II in cell extracts and conditioned media obtained from cardiomyocytes and fibroblasts were quantified by radioimmunoassay. The amounts of ANG I and II detected in cardiomyocyte cultures (1.48 x 10(6) cells/dish) were 32.2 +/- 16.2 (n = 4) and 6.2 +/- 2.9 (n = 4) ng/10(6) cells, respectively. The amounts of ANG I and II detected in the media conditioned by a 48-h exposure to cardiomyocytes were 5.2 +/- 1.2 (n = 3) and 2.1 +/- 1.2 (n = 3) ng/10(6) cells, respectively. The amounts of ANG I and II detected in fibroblast cultures (5.38 x 10(6) cells/dish) were 34.8 +/- 4.9 (n = 4) and 8.0 +/- 3.5 (n = 4) ng/10(6) cells, respectively. The amounts of ANG I and II obtained from media conditioned by a 48-h exposure to fibroblasts were 4.7 +/- 0.6 (n = 4) and 3.3 +/- 2.1 (n = 4) ng/10(6) cells, respectively. The identity of the radioimmunoassayable materials as ANG I and II peptides was confirmed in cardiomyocytes using an in vitro bioassay based on displacement of 125I-ANG II from receptor binding sites in cardiac membranes prepared from neonatal pig heart. Identification of ANG I and II and ACE in vitro in cultures of cardiac myocytes and fibroblasts supports the hypothesis that there is an intracardiac renin-angiotensin system that produces these peptides.

Angiotensin I↗
PubMed1991

Establishment of reference methods for lipids, lipoproteins and apolipoproteins.

Reference methods for lipids, lipoproteins, and apolipoproteins have been developed for use as part of an accuracy base for institutional, national, or international reference systems. A widely accepted reference method exists only for total cholesterol. Well described interim or institutional in-house reference methods have been established for the other lipids, lipoproteins, and apolipoproteins. The major criteria for a reference method are 1) scientific basis, 2) sound principles, 3) available calibration and control materials, 4) traceability to a definitive method or a point of reference, and 5) applicability to reference materials that provide traceability to clinical methods and transferability to other reference laboratories. The total cholesterol reference method of the U.S. National Reference System demonstrates how a reference method can be developed and applied. Reference methods now available can lead to an accepted international accuracy base for the clinically useful lipid, lipoprotein, and apolipoprotein measurements.

Apolipoprotein A-I↗
PubMed1991

Factors influencing the accuracy of the national reference system total cholesterol reference method.

Previous comparisons between the Reference and Definitive Methods for measuring serum cholesterol have demonstrated a small but persistent positive bias in the Reference Method, averaging about +1.6%. Here we describe the results of further investigations designed to better characterize the nature of this bias. Analysis of a well-characterized model serum sample (SRM 909) suggests that more than half of the difference in cholesterol values determined by the two methods is the result of small contributions from cholesterol precursor sterols and phytosterols, which are also measured for the Reference Method. An additional significant contribution may be from cholesterol oxidation products, particularly 7-hydroxycholesterol isomers, which are active in the Liebermann-Burchard reaction. The 7-hydroxycholesterol in SRM 909, most of which appeared to be already present in the serum rather than formed during saponification, may account for as much as 20% of the observed difference between the methods. Contributions from other possible sources, including impurities in the cholesterol standard and incomplete saponification of cholesteryl esters, are very small. Because the observed bias is both quite small and consistent among samples, the cholesterol Reference Method continues to meet all of the requirements generally expected for a dependable and effective Reference Method.

Carbon Isotopes↗
PubMed1991

Clinical issues in cholesterol testing.

Lipid investigators have begun to examine the biological sources of variation in serum cholesterol levels and to seek ways to accurately measure the total cholesterol (TC) level in the serum of a patient. A person's TC level varies primarily because of the effects from seasonal changes, behavioral changes, and illness. Results of studies of the effect of seasonal changes indicate that serum TC and obesity increase during winter and decrease during summer. Behavioral sources of variation include diet, alcohol intake, smoking, and exercise. Clinical sources of TC level variation include all illnesses. The physician can help control sources of variation by recognizing their causes, by advising of the effect that behavioral risk factors have on cholesterol levels, and by using the average of results for multiple specimens to estimate the true value of serum cholesterol in a patient.

Behavior↗
PubMed1990

Effects of analytical method and lyophilized sera on measurements of apolipoproteins A-I and B: an international survey.

In 1987 a collaborative study was initiated with 140 laboratories worldwide to evaluate the effects of analytical method and lyophilization on the measurement of different concentrations of apolipoproteins (apo) A-I and B in four lyophilized serum pool samples. This survey confirmed that the lyophilized apo Reference Material of the International Union of Immunological Societies (IUIS) is useful for apo A-I assays as an international serum-based reference material, because among-method variation is negligible. The apo A-I concentration value of 1.24 g/L is now assigned to the IUIS Reference Material (CDC 1883) by a Centers for Disease Control RIA in-house reference method. Use of lyophilized serum preparation as a reference material for some modes of apo B measurement is questionable because of lyophilization and matrix effects. Both radial immunodiffusion and liquid immunoprecipitin methods demonstrated bias in measured apo B concentrations, compared with overall method-weighted means values on the IUIS Reference Material. Because of the uncertainty associated with LDL primary standard, protein analysis, and concentration differences among analytical methods, assigning a single apo B concentration value to the IUIS Reference Material appears inadvisable at present.

Analysis of Variance↗
PubMed1990

Reference system for cholesterol measurements.

A reference system for cholesterol measurement is necessary to assure accuracy of cholesterol measurements by clinical, research, and manufacturers' laboratories. Such a reference system is based on the collaboration of laboratory and clinical professionals, research groups, professional societies, government groups, and manufacturers of diagnostic products. Essential components include a definitive method, a reference method, and commutable reference materials that are accurately labeled and have long-term stability. A mechanism by which clinical, research, and manufacturers' laboratories can establish traceability to the reference system is also needed. In the United States, the NRS/CHOL was organized as part of the National Reference System for the Clinical Laboratory. The major organizational components of the NRS/CHOL include the National Institute for Standards and Technology, the CDC, the CRMN, the CAP, the AAB, regional reference programs, and manufacturers of cholesterol diagnostic products. The NIST maintains an isotope dilution-mass spectrometer definitive method and distributes certified reference materials. The CDC maintains a modified Abell-Levy-Brodie-Kendall reference method and offers a CDC-NHLBI Lipid Standardization Program; the CRMN provides reference method analyses on specimens furnished by manufacturers and clinical or research laboratories; CAP, AAB, and regional reference programs provide either proficiency testing, quality assurance programs, or both; and manufacturers assure that results on diagnostic products are the same as those achieved when using fresh patient specimens and the NRS/CHOL reference method. The NRS/CHOL has contributed much to the success of clinical epidemiologic and research and development investigations in coronary heart disease.

Chemistry, Clinical↗
PubMed1990

Impact of protein measurements on standardization of assays of apolipoproteins A-I and B1.

In 1989 the Committee on Apolipoproteins of the International Federation of Clinical Chemistry and the Centers for Disease Control conducted an international survey of total-protein measurements of isolated low-density lipoproteins (LDL) and delipidated high-density lipoproteins (HDL), and of their relationships to the National Institute of Standards and Technology (NIST) bovine serum albumin (BSA) Standard Reference Material (SRM). Most of the 93 apolipoprotein laboratories surveyed use the Lowry total-protein method. Results reported with the LDL preparations demonstrated a large bias and variation among methods; those with delipidated HDL were not as great, but were similar to those for BSA. Performance improved appreciably with use of the Lowry-sodium dodecyl sulfate method and the NIST BSA SRM for protein measurement. The total CVs, including among-laboratory and within-laboratory errors, averaged approximately 50% and 23% for LDL, 17% and 11% for HDL, and 18% and 11% for BSA solutions by all methods and by the Lowry methods, respectively. Regardless of the methods used, greater variability of the protein measurements was seen with the normally occurring LDL than with the nonlipoprotein BSA or delipidated HDL. The mean CV values for all samples among laboratories averaged between 10% and 15% with the modified Lowry methods; the biuret method gave the highest among-laboratory CV, 34%; the Kjeldahl had the lowest, 7.7%. Use of the same methodology and primary nonapolipoprotein standard is essential for comparability of protein results for apolipoprotein primary standard solutions. This is especially true for apolipoprotein B, because its inherent properties and lability make protein analysis difficult. This study supports the use of a standardized selected Lowry-sodium dodecyl sulfate method traceable to quantitative amino acid analysis as a point of reference for determining the protein concentration of primary calibration reference materials for apolipoproteins.

Apolipoproteins A↗
PubMed1990

College of American Pathologists-Centers for Disease Control collaborative study for evaluating reference materials for total serum cholesterol measurements.

Several recent studies to evaluate the performance of laboratory instruments have shown that with some instrument systems processed (lyophilized, frozen, and stabilized) materials exhibit matrix effects that cause the assay for cholesterol to respond differently for them than for patient specimens. To understand this phenomenon better the College of American Pathologists, Northfield, III, and the Centers for Disease Control, Atlanta, Ga, have conducted a collaborative study with 44 laboratories where 16 instruments manufactured by nine companies are evaluated. The purposes were to assess measurement variation on several reference materials used for standardizing total cholesterol measurements and to evaluate a new stabilized liquid serum as a potential reference material. Lypophilized, frozen, fresh-frozen, and stabilized materials at three concentrations were measured for total cholesterol. The results show that the average coefficient of variation of measured total cholesterol for all instruments, laboratories, vials, and replicates is 3.6% to 4.1% for each of the materials measured (excluding the results for one instrument). For one instrument, however, significant bias was found on the stabilized liquid serum material. Results from the fresh-frozen materials indicate that the instrument systems evaluated allow laboratories to attain the National Cholesterol Education Program analytical performance goals.

Analysis of Variance↗
PubMed1990

A comparison of results for cholesterol in human serum obtained by the Reference Method and by the Definitive Method of the National Reference System for cholesterol.

Here we compare the Reference Method (I) and the Definitive Method (II) for measurement of cholesterol in serum. For pure cholesterol solutions, values by I agree with values by II, but for fresh, frozen, or lyophilized sera, values by I average 1.6% higher than values by II. We conclude that an undetected interference is associated with I. However, the observed difference does not diminish the usefulness of I as an accuracy base for cholesterol measurements, because it is clinically insignificant at present.

Blood Preservation↗
PubMed1989

Progress in lipid reporting practices and reliability of blood cholesterol measurement in clinical laboratories in Nebraska. Efforts to align results with the Centers for Disease Control, and feasibility of meeting National Cholesterol Education Program Guidelines.

The National Cholesterol Education Program has recommended that all laboratories be consistent, precise, and accurate in the reporting and measurement of blood cholesterol levels. In a follow-up to a 1984 survey study, we assessed the changes in reporting procedures for measurements of blood lipid levels in 16 clinical laboratories in Nebraska. Using human serum reference materials of known cholesterol concentrations provided by the Centers for Disease Control, we also assessed the precision and accuracy of measurement of blood cholesterol levels in clinical laboratories in Nebraska. Fourteen of the 16 laboratories restudied in 1987 had altered the reference range for total serum cholesterol since 1984, 86% of whom lowered the upper limit of the reference range. Eleven of 16 laboratories expressed reference ranges for total serum cholesterol in terms of patient age in 1987, while only 7 of 20 did in 1984. Gender-based reference ranges increased from 0 to 5 from 1984 to 1987. Similar trends were seen in the reporting of high-density lipoprotein cholesterol and triglyceride concentrations. Reporting procedures varied greatly; only 1 laboratory used National Cholesterol Education Program risk levels for measuring total serum cholesterol levels. Fifteen laboratories met the National Cholesterol Education Program recommendation for precision (coefficient of variation, less than or equal to 5%) and 78% of laboratories obtained results that satisfied the current recommendation for accuracy (within 5% of "true value," as determined by the Centers for Disease Control).

Adult↗
PubMed1989

Cholesterol-based personal risk assessment in coronary heart disease.

Using data from the National Health and Nutrition Examination Survey (NHANES II) 1976-1980, we demonstrate how cross-sectional total serum cholesterol surveillance data can be used by an individual to assess current and future personal cholesterol risk status. We propose statistical models, based on a person's current measured cholesterol level and the relationship between cross-sectional age and cholesterol percentile estimates, that will allow prediction of future cholesterol levels or the age at which specified cholesterol risk levels will be reached if no cholesterol-altering intervention is taken. These models incorporate the observed variation in the NHANES II data and expected intraperson biological variation and intralaboratory analytical variation. We illustrate the adequacy of the models using data from the longitudinal Framingham Study.

Adult↗
PubMed1989

The Centers for Disease Control-National Heart, Lung and Blood Institute Lipid Standardization Program. An approach to accurate and precise lipid measurements.

In collaboration with the National Heart, Lung, and Blood Institute, the CDC has supported programs for standardizing lipid measurements for more than 30 years. These programs were begun because comparable and accurate quantitative measurements were needed for epidemiologic studies of coronary heart disease. Since the first program was initiated, over 500 national and international laboratories have participated in the various CDC lipid standardization programs. The cornerstone of these standardization programs has been an accuracy base of lipid reference materials and methods developed by CDC. Specifically, CDC has developed human, serum-based reference materials for cholesterol, HDL, triglyceride, and apolipoproteins A-I and B and reference methods for total cholesterol, HDL, and triglyceride. The CDC reference method for cholesterol has been adopted as the national reference method for cholesterol by the National Reference System for the Clinical Laboratory Council of the National Committee for Clinical Laboratory Standards. The approved CDC reference method along with an approved NBS definitive method, an approved NBS certified Reference Material, and the CDC certified serum-based secondary reference materials make up the accuracy base for serum cholesterol measurements in the United States, and together they are recognized as the National Reference System for Cholesterol. The NCEP Laboratory Standardization Panel recommends that cholesterol measurements made by all clinical laboratories should be standardized so that cholesterol values are traceable to the National Reference System for Cholesterol. In support of the NCEP's efforts, CDC will establish a standardization program permitting the laboratory and manufacturing community to trace cholesterol measurements and the development of cholesterol diagnostic products back to the national reference system. The major emphasis of this standardization effort is to establish a network of reference method laboratories (1) to assign cholesterol values to all commercially prepared lots of calibrators and control materials and (2) to provide reference measurements on individual "fresh" human serum specimens to manufacturers and clinical laboratories. CDC is also working to (1) provide reference materials to manufacturers, (2) collaborate with NBS to maintain documentation of the national reference system accuracy base, (3) cooperate with proficiency testing organizations to assist in the accurate labeling of reference materials, and (4) provide training and education pertinent to cholesterol standardization.(ABSTRACT TRUNCATED AT 400 WORDS)

Centers for Disease Control and Prevention, U.S.↗
PubMed1988

Standardization of lipid, lipoprotein, and apolipoprotein measurements.

Accurate laboratory measurement of serum cholesterol has become a national public health priority. National proficiency testing surveys indicate that laboratory inaccuracy in cholesterol testing is more of a problem than precision. Like precision, accuracy is a function of multiple pre-analytical and analytical sources of variation. Controlling pre-analytical sources of variation helps minimize such sources of variation as intraperson biological, behavioral, and clinical differences, and variations caused by sample collection, handling, and shipping. Standardization of analytical sources of variation helps to achieve and maintain desirable analytical performance, accurate reporting, and correct interpretation of a reported cholesterol result. The intraperson total variation in lipoproteins and their constituents is of primary interest when one is interpreting a single result or a series of results from a single person. The mean of multiple specimens from the same person is required if one is to obtain an accurate value for intraperson total cholesterol and minimize pre-analytical sources of variation. Standardizing analytical sources of variation in some instrument systems requires standardizing results by using "fresh" patients' specimens.

Apolipoproteins↗